Category Archives: Stem Cells

Changing the number of chromosomes an animal has can take millions of generations to happen in nature through the course of evolution and now, scientists have been able to make these same changes in lab mice in a relative blink of an eye.

The new technique using stem cells and gene editing is a major accomplishment, and one that the team is hoping will reveal more about how the rearrangement of chromosomes can influence the way that animals evolve over time.

It's in chromosomes those strings of protein and DNA inside cells that we find our genes, inherited from our parents and blended together to make us who we are.

For mammals like mice and us humans, chromosomes typically come paired. There are exceptions, such as in sex cells.

Unfertilized embryonic stem cells are usually the best starting place for tinkering with DNA. Lacking that additional set of chromosomes provided by a sperm cell, though, deprives the cells of an important step in negotiating which genes in which chromosomes will be marked active to do the job of building a body.

This process called imprinting was a stumbling block for engineers keen to restructure large chunks of the genome.

"Genomic imprinting is frequently lost, meaning the information about which genes should be active disappears in haploid embryonic stem cells, limiting their pluripotency and genetic engineering," says biologist Li-Bin Wang from the Chinese Academy of Sciences.

"We recently discovered that by deleting three imprinted regions, we could establish a stable sperm-like imprinting pattern in the cells."

Without those three naturally imprinted regions, lasting chromosome fusion was possible. In their experiments, the researchers fused two medium-sized chromosomes (4 and 5) and the two largest chromosomes (1 and 2) in two different orientations, resulting in three different arrangements.

The fusion of chromosomes 4 and 5 was the most successful in terms of the genetic code being passed on to the mice offspring, although breeding was slower than normal.

One of the 1 and 2 fusions produced no mice offspring, while the other produced mice offspring that were slower, larger, and more anxious than those from the fusion of chromosomes 4 and 5.

According to the researchers, the drops in fertility are down to how the chromosomes separate after alignment, which doesn't happen in the normal way. It shows that chromosomal rearrangement is crucial to reproductive isolation a key part of species being able to evolve and stay separate.

"The laboratory house mouse has maintained a standard 40-chromosome karyotype or the full picture of an organism's chromosomes after more than 100 years of artificial breeding," says biologist Zhi-Kun Li, also from the Chinese Academy of Sciences.

"Over longer time scales, however, karyotype changes caused by chromosome rearrangements are common. Rodents have 3.2 to 3.5 rearrangements per million years, whereas primates have 1.6."

To put this into context, rare leaps in chromosomal rearrangement have helped direct the evolutionary paths of our own ancestors. Chromosomes that remain separate in gorillas, for instance, are fused into one in our human genome.

Those types of changes can occur once every few hundred millennia. While the genetic edits made here in the lab were on a relatively small scale, the signs are that they could have some dramatic effects on the animals involved.

It's still early days this is a scientific first after all but further down the line, there might be the opportunity to correct misaligned or malformed chromosomes in human bloodlines. We know that in individuals, chromosome fusions and relocations can lead to health problems including childhood leukemia.

"We experimentally demonstrated that the chromosomal rearrangement event is the driving force behind species evolution and important for reproductive isolation, providing a potential route for large-scale engineering of DNA in mammals," says Li.

The research has been published in Science.

Read this article:
Scientists Just Genetically Edited a Million Years of Evolution Into Mouse DNA - ScienceAlert

A hospital in Kanpur became the first in India to perform fat-derived stem cell transplant for diabetic patients.

A 50-year-old man became the first recipient of derived stem cell transplant in the country. (Photo: India Today)

The LLR government hospital in Kanpur has become the first hospital in the country to perform the first fat-derived stem cell transplant. This has come as good news for all the patients with type 2 diabetes who have to take insulin frequently.

In this method, stem cells are extracted from waist and abdominal fat and injected into the patient's muscles and blood cells. This will help the patient's pancreas (beta cells) to release normal amount of insulin.

The 50-year-old male recipient of this first adipose-derived stem cell transplant in the country has been suffering from type 2 diabetes for the past five years.

According to doctors, the cost of this transplant so far is Rs 2.5 lakh and in the near future the cost is expected to come down and the treatment will be cheaper for many people suffering from type 2 diabetes.

The stem cell approach will continue to offer a new ray of hope to patients and their families.

This operation is called fat-derived step transfer which takes place after removing the fatty tissue from the patient himself and then processing it with patented technology from Australia. So, the cost of the machine is Rs 1 crore and operation cost is Rs 2,52,000, said Dr Sanjay Kala, Principal of GSVM Medical College, Kanpur.

So far, we have only read about the response to stem cell transplant in diabetic patients in books. But this has been done for the first time in the country. Insulin and other supplements prove to be expensive in the long term. With this, we can give a pill or dose of stem cell therapy and a patient with diabetes can be cured, added Dr Sanjay Kala.

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Kanpur hospital is Indias first to perform fat-derived stem cell transplant for diabetic patients - India Today

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Canadian Blood Services Stem Cells for Life

Creating an embryo from cells other than sperm and egg cells and then growing them outside the uterus is an area of study that has developed significantly over the past 5 years. How long until we unlock the black box of human embryology?

This month, researchers announced that they have been culturing a mouse embryo model made entirely out of embryonic stem cells and without the use of a sperm and egg, or a uterus, for 8.5 days, about 2 days longer than previous experiments had achieved.

Genetic analysis revealed that the structures and cell activity in these embryo models were 95% similar to real mouse embryos and functional. This suggests that these models were similar enough to natural embryos that they could be studied to gain insight into how they work.

Research on both mice and human embryos can offer insight into the mechanisms that allow them to divide, implant, and develop. However, being able to build them from scratch helps researchers bypass potentially expensive and unethical experiments on embryos and also helps them verify if assumptions about how they work are correct.

A paper recently published in Cell outlines the achievement by researchers in Prof. Jacob Hannas laboratory at the Weizmann Institute of Science in Rehovot, Israel.

This is the latest step in a long line of incremental steps in recent years to create an embryo from scratch in the lab.

Prof. Hannas team had already published details of one particularly important part of the puzzle last year in Nature, when they outlined the process they had used to grow embryo models outside of a uterus.

The system they developed uses bottles filled with liquids that act as a culture for the cells, which can rotate or remain static at different points of development.

In an email to Medical News Today, Prof. Hanna noted: Since we know what it takes to support the growth of [natural mouse embryos] outside the uterus (device and conditions), we can finally test whether and which stem cells can generate an embryo ab initio [from the start] only from stem cells.

We couldnt do that before because how are you going to grow a synthetic embryo if you dont know how to grow a natural embryo? Low and behold indeed, the same device, the same media conditions, and the same parameters allowed aggregates of 27 cells of pluripotent stem cells to reach day 8.5-stage embryos when placed in this device after 8 days.

Prof. Jacob Hanna

The device and the media were critical. These embryos are whole embryos they have [a] yolk sac and placenta. But remarkably, we did not use placenta stem cells and yolk sac stem cells, but showed that everything can be made exclusively from naive pluripotent embryonic stem or induced pluripotent stem cell lines that are routinely expanded in labs around the world, he explained.

This was remarkable because previously, researchers had made embryo models that began to form the placenta, egg yolk, and amnion using a mixture of embryonic stem cells and stem cells taken from the trophoblast layer. This is the layer that normally differentiates into the placenta in embryos.

However, the failure rate in this latest set of experiments was high, with just 50 of 10,000 of these cell mixtures forming first into spheres and then into more egg-shaped structures such as an embryo.

Not only did these embryo models start to produce the structures that would support a pregnancy, but by the end of the 8.5 days in which they grew, they had formed a beating heart, blood stem cell circulation, a head region with folds, a neural tube and the beginnings of a gut tube.

The same week this paper appeared in Cell, the University of Cambridge-based laboratory of Prof. Magdalena Zernicka-Goetz published two papers on a preprint server: shared here and here. In fact, Prof. Zernicka-Goetzs team shared the latter on the same day the Cell study was published.

This paper outlines how the researchers from the Cambridge lab had observed similar organ structures start to form in their own research using embryo models.

Prof. Zernicka-Goetz told MNT in an interview that these papers would appear in peer-reviewed journals in the coming weeks and that their final versions were currently under embargo.

So it is [a] step by step [process] [] our paper is going to show even further developments, she told us.

This latest finding builds on the previous work of other laboratories and teams, both those of Prof. Zernicka-Goetz and others, said Prof. David Glover, her husband.

Profs. Glover and Zernicka-Goetz have teams at Cambridge and CalTech. They have carried out research together and appear as co-authors on one of the papers due to be published soon.

He told MNT in an interview: I think you have to go back to Magdas paper published in 2017, [whose] senior author was Sarah Harrison, which establishes the principle of being able to make an embryo-like structure using a mixture of extraembryonic cells and embryonic cells.

Extraembryonic cells include key components forming extraembryonic tissues, which are crucial to maintaining embryo survival. Extraembryonic tissues include the placenta, yolk sac, and amnion.

Being able to produce embryo models that feature the start of development of these tissues is so important because they help initiate the signaling that helps the embryo model develop and self-assemble much as a naturally developing embryo would, Prof. Glover noted.

The fact is that, because our own embryos develop inside the womb, they require extraembryonic tissues to develop properly. And those extraembryonic tissues have two functions. They provide, of course, a structural basis, they provide a yolk sac, [and] they provide the placenta, he explained.

But before they get to that stage, they also provide signals to the embryo to tell it how to properly develop. And if you dont have those signals there, then the embryo doesnt develop properly, the researcher added.

These particular models were just one type of embryo model currently being developed, said Prof. Glover.

Researchers have also developed other models, such as blastoids, which attempt to recreate the pre-implantation blastocyst stage of the embryo, and gastruloids, which do not have any extraembryonic tissues, and as a result, tend not to have a brain region.

Dr. Nicholas Rivrons laboratory at the Institute of Molecular Biotechnology at the Austrian Academy of Sciences, Vienna, Austria, has worked on developing embryo models to gain greater insight into the pre-implantation stage.

His group published a 2018 key paper in Nature. It outlined how they developed mouse embryo models using embryonic stem cells and stem cells from the trophoblast layer to create blastoids that could be implanted into the uterus of a mouse for a couple of days.

Then, in December 2021, the same team published another paper in Nature. This time, they outlined how they had created embryo models to the blastocyst stage made from human pluripotent stem cells, which they had induced to become able to differentiate into different types of cells.

Speaking to MNT, Dr. Rivron said: For the next stages of investigation, we need to actually understand how those embryos can be combined with the uterine cells in order to understand the processes of implantation into the uterus and how this can develop our knowledge to solve various health challenges of family planning, fertility decline, also the origin of diseases.

While the embryo models described in the latest paper demonstrated they had self-organized to form some structures that would go on to form the placenta, these embryo models were limited by how much further they could grow without one, said Dr. Rivron.

The limitation is the placenta the placenta is extremely important, he noted, due to the fact that it provides the nutrients and oxygen to the embryo that are essential for it to grow and develop further.

The latest paper also confirmed that the very first stages of organ development, known as organogenesis, could be observed in these model embryos.

This has typically been difficult to observe, as it typically occurs in the uterus. However, by establishing a process to develop these embryo models in the laboratory, the differentiation of the cells, the genetic control of this differentiation, and the environment needed for typical development can all be studied.

The latest paper used mouse embryonic stem cells to develop the model embryos, which will require ethical approval. By contrast, human embryo research is extensively regulated.

Guidelines for this regulation are released by the International Society for Stem Cell Research (ISSCR) approximately every 5 years, with the last set of guidelines released last year. This guidance addressed the existence of stem cell-derived embryo models and the possibility of chimeric embryo models built using cells from different species alongside human cells.

While it may prove technically possible to grow organs using embryo models, Dr. Rivron pointed out that this may not be necessary or, indeed, ethically desirable.

He pointed instead to the development of organoids, stem cell-derived models of organ tissues that can be used to investigate cellular behavior, and perhaps the development, of organs too.

In fact, a paper outlining how researchers at Harvard Unversity had bioengineered structures of the human heart appeared in Science in the same week as the latest article on embryo models.

Dr. Rivron contributed to the latest set of ISSCR guidelines and told MNT: If you want to study organogenesis or create organs, the political principle is that you have to use, morally, the least problematic way of studying these, and organoids offer a way to do this.

Both the development of organoids and embryo models have come in leaps and bounds in the past 5 years, and their basis, new genomic approaches we can use to understand and recreate mammalian structures, are similar.

It will be interesting to see how the disciplines converge in years to come, to give us an even greater set of tools to unlock the black box of our development.

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Scientists say they have created 'embryos' without sperm or eggs - Medical News Today

The remarkable power of stem cells - which can be programmed to become almost any type of cell in the body - means they are key to many scientific studies.

Increasingly, they are also being used for new cell-based therapies to treat a range of diseases.

While originally we could only get stem cells from embryos, now we can derive them from a range of adult tissues, including skin or blood, using Nobel Prize-winning technology.

But Cambridge researchers have found DNA damage caused by factors such as ultraviolet radiation affected 72 per cent of the stem cell lines they studied that had been derived from human skin cells. This has important implications for research and medicine.

Prof Serena Nik-Zainal, from the Department of Medical Genetics at the University of Cambridge, said: Almost three-quarters of the cell lines had UV damage. Some samples had an enormous amount of mutations sometimes more than we find in tumours. We were all hugely surprised to learn this, given that most of these lines were derived from skin biopsies of healthy people.

Induced pluripotent stem cells (iPSCs), as those derived from other cell types or tissues are known, hold huge potential for tackling diseases, including rare conditions.

It is even suggested that iPSCs programmed to grow into nerve cells could be used to replace those lost to neurodegeneration in diseases such as Parkinsons.

The new research, published in Nature Genetics, represents the largest genetic study to date of iPSCs to date.

Dr Foad Rouhani, who carried out the work while at the University of Cambridge and the Wellcome Sanger Institute, said: We noticed that some of the iPS cells that we were generating looked really different from each other, even when they were derived from the same patient and derived in the same experiment.

The most striking thing was that pairs of iPS cells would have a vastly different genetic landscape one line would have minimal damage and the other would have a level of mutations more commonly seen in tumours.

One possible reason for this could be that a cell on the surface of the skin is likely to have greater exposure to sunlight than a cell below the surface and therefore eventually may lead to iPS cells with greater levels of genomic damage.

[Read more: Evidence of new causes of cancer uncovered as genomic data of 12,000 NHS patients is studied by University of Cambridge researchers]

DNA comprises three billion pairs of nucleotides - molecules represented by the letters A, C, G and T.

Damage from sources such as ultraviolet radiation or smoking leads to mutations, meaning a letter C might change to T, for example.

Studying the mutational fingerprints on our DNA can reveal what is responsible for the damage.

An accumulation of mutations can have a profound effect on cell function and in some cases lead to tumours.

Using whole genome sequencing, the researchers inspected the entire DNA of stem cell lines from different sources, including the HipSci cohort at the Wellcome Sanger Institute.

They found blood-derived iPSCs - which are increasingly common, due to the ease with which blood can be taken - also carried mutations but at a lower level than skin-derived iPS cells, and they had no UV damage.

Some 26.9 per cent of them, however, carried mutations in a gene called BCOR, which is an important gene in blood cancers.

Next the researchers investigated whether these BCOR mutations had any functional impact.

They differentiated the iPSCs, turning them into neurons and tracking their progress along the way.

[Read more: 4m funding for Cambridge scientists under Cancer Grand Challenges initiative]

Dr Rouhani said: What we saw was that there were problems in generating neurons from iPSCs that have BCOR mutations they had a tendency to favour other cell types instead. This is a significant finding, particularly if one is intending to use those lines for neurological research.

Analysis of the blood samples showed the BCOR mutations were not present within the patient.

So it seemed that the process of culturing cells increased the frequency of the mutations, which could have implications for other researchers working with cells in culture.

Typically, scientists using cell lines will screen them at the chromosomal level checking, for example, that the requisite 23 pairs of chromosomes are present.

Such analysis would not pick up the potentially major problems that this new study has identified, however,

The researchers warn that without looking in detail at the genomes of these stem cells, researchers and clinicians would be unaware of the underlying damage in them.

The DNA damage that we saw was at a nucleotide level, explained Prof Nik-Zainal. If you think of the human genome as like a book, most researchers would check the number of chapters and be satisfied that there were none missing. But what we saw was that even with the correct number of chapters in place, lots of the words were garbled.

Using whole genome sequencing, however, would enable errors to be discovered at the outset..

The cost of whole genome sequencing has dropped dramatically in recent years to around 500 per sample, though it's the analysis and interpretation that's the hardest bit, said Prof Nik-Zainal.

If a research question involves cell lines and cellular models, and particularly if we're going to introduce these lines back into patients, we may have to consider sequencing the genomes of these lines to understand what we are dealing with and get a sense of whether they are suitable for use.

Dr Rouhani adds: In recent years we have been finding out more and more about how even our healthy cells carry many mutations and therefore it is not a realistic aim to produce stem cell lines with zero mutations.

The goal should be to know as much as possible about the nature and extent of the DNA damage to make informed choices about the ultimate use of these stem cell lines.

If a line is to be used for cell based therapies in patients for example, then we need to understand more about the implications of these mutations so that both clinicians and patients are better informed of the risks involved in the treatment.

The research was funded by Cancer Research UK, the Medical Research Council and Wellcome, and supported by NIHR Cambridge Biomedical Research Centre and the UK Regenerative Medicine Platform.

Continued here:
Many stem cell lines used for research and therapies carry large number of mutations, Cambridge researchers find - Cambridge Independent

The group of scientists planned to take stem cells from a living marsupial species with a similar DNA, before using gene-editing technology to revive the extinct species - or a close approximation of it

Image: Popperfoto via Getty Images)

Scientists are launching a project aiming to bring the Tasmanian tiger back from extinction through stem cells and gene-editing technology.

The last of the extinct marsupials, which are officially called thylacines, died in the 1930s.

The team behind the project said the tiger could be recreated using stem cells and gene-editing technology.

If successful, the thylacine would be the first of its kind to be reintroduced to the wild in 10 years time.

However, some experts are sceptical, suggesting de-extinction is a thing of science fiction.

According to BBC reports , the thylacine was given its nickname of Tasmanian tiger due to the stripes along its back.

However, it was actually a marsupial, the variety of Australian mammal that raises its young in a pouch.

Image:

The mixed group of Australian and US scientists planned to take stem cells from a living marsupial species with a similar DNA, before using gene-editing technology to revive the extinct species - or a close approximation of it.

The project would require a number of scientific breakthroughs in order to be successful.

If carried out, it would represent a remarkable achievement for the researchers attempting it.

Professor Andrew Pask, who is leading the research from the University of Melbourne, said: "I now believe that in 10 years' time we could have our first living baby thylacine since they were hunted to extinction close to a century ago," .

Tasmanian tiger numbers declined when humans arrived in Australia tens of thousands of years ago.

The population dwindled even further when humans arrived in Australia tens of thousands of years ago and again when dingoes, a species of wild dog, appeared.

Image:

Tasmanian tigers eventually only roamed free on the island of Tasmania, where they were ultimately hunted to extinction.

The last captive Tasmanian tiger died in 1936, at Hobart Zoo.

De-extinction and the science behind it has its critics, with Associate Professor Jeremy Austin from the Australian Centre for Ancient DNA, calling de-extinction fairytale science.

Professor Austin, speaking to the Sydney Morning Herald, said the project was "more about media attention for the scientists and less about doing serious science".

The idea to bring back the Tasmanian tiger has been around for more than 20 years.

The Australian Museum started to pursue a project to clone the animal back in 1999 and various attempts have been made at intervals ever since either to extract or rebuild viable DNA from samples.

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Scientists hope to revive extinct mammal through stem cells and gene-editing in a first - The Mirror

The recent pandemic has highlighted the need to remain healthy. Illnesses and other health conditions can be major obstacles to enjoying a happy and fruitful life, thus the importance of ensuring that our bodies are at the best state they could be.

This has led to the rise of different treatment modalities, with stem cell therapy being one of the most sought after. Widely considered as the bodys raw material, stem cells develop into different types of cells which would replace damaged ones, resulting in a healthier body. However, these stem cell therapies can be prohibitively expensive.

GFoxx International hopes to bring stem cell therapy to a wider audience with the launch of its latest product, Elixir Placenta. Made from New Zealand Deer Placenta, Elixir Placenta combines the benefits of stem cell therapy, DNA therapy and anti-inflammatory therapy in one soft gel capsule.

The ethical barriers regarding stem cell therapy are avoided by the use of deer placenta.

Studies have shown that deer placenta is closely similar to the human placenta. These are harvested from New Zealand deer that live and grow in pristine and pollution-free surroundings.

After harvesting, deer placenta is freeze-dried and processed along with 13 other natural products including Angelica Sinesis, grape and olive extract, D-Ribose, yeast extract, Squalene oil, MCT, fermented red ginseng, rice bran oil, sea buckthorn oil, Rhodiola Rosea, Black currant seed oil, Fenugreek and Nigela seed oil.

GFoxx claims that these ingredients work in synergy, resulting in a capsule that offers stem cell therapy, DNA therapy, and anti-inflammatory therapy. It can be used as a supplement for treating arthritis, multiple sclerosis, heart attack, acute lymphoblastic leukemia, and other chronic diseases. The anti-aging supplement also promotes cell growth and boosts immunity.

Elixir Placenta is exclusively distributed by Gfoxx International. Visit gfoxxint.com , GFOXXCompanyOffical on Facebook and GFOXXOfficial on Instagram.

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Stem cell therapy in capsule form - Malaya

Clinical Neurosciences

Location: Southampton General HospitalSalary: 22,149 to 25,642Part Time (21.4 hours per week) Fixed term 13 MonthsClosing Date: Monday 29 August 2022Interview Date: To be confirmedReference: 1939422FC

A human stem cell culture technician position is available in the Vision Group within the Faculty of Medicine at the University of Southampton. The successful candidate will join a strong interdisciplinary team investigating the genetic basis of visual system development and disease with a strong translational focus. This will include the development of novel methods combining human stem cell biology, genetic analysis and genome-engineering technology applications. The post requires excellent cell culture technique, communication and organizational skills, including detailed recordkeeping, computer literacy, and the ability to contribute to method development and validation. After initial training, this individual is expected to perform protocols independently with minimal guidance, with accuracy, discretion and good judgment, and will assist the PIs (Dr Jrn Lakowski; Prof Andrew Lotery) with the collection and analysis of data by conducting specific experiments.

General position requirements include human pluripotent stem cells handling, performing CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) -based methods, assisting in maintaining equipment, managing laboratory supplies, lab upkeep, and other general responsibilities in laboratory operation as assigned or directed, in order to meet the goals and objectives of the laboratory group.

Application Procedure

You should submit your completed online application form at https://jobs.soton.ac.uk. The application deadline will be midnight on the closing date sated above. If you need any assistance, please call Jane Sturgeon (Recruitment Team) on +44 (0) 23 8059 2750 or email recruitment@soton.ac.uk. Please quote reference 1939422FC on all correspondence.

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Cell Culture Technician Pluripotent Stem Cell Biology and Genome Editing job with UNIVERSITY OF SOUTHAMPTON | 305107 - Times Higher Education

Viruses that cause respiratory diseases like the flu and COVID-19 can lead to mild to severe symptoms within the first few weeks of infection. These symptoms typically resolve within a few more weeks, sometimes with the help of treatment if severe. However, some people go on to experience persistent symptoms that last several months to years. Why and how respiratory diseases can develop into chronic conditions like long COVID-19 are still unclear.

I am a doctoral student working in the Sun Lab at the University of Virginia. We study how the immune system sometimes goes awry after fighting off viral infections. We also develop ways to target the immune system to prevent further complications without weakening its ability to protect against future infections. Our recently published review of the research in this area found that it is becoming clearer that it might not be an active viral infection causing long COVID-19 and similar conditions, but an overactive immune system.

Keeping your immune system dormant when there isnt an active infection is essential for your lungs to be able to function optimally.

Your respiratory tract is in constant contact with your external environment, sampling around 5 to 8 liters (1.3 to 2 gallons) of air and the toxins and microorganisms in it every minute. Despite continuous exposure to potential pathogens and harmful substances, your body has evolved to keep the immune system dormant in the lungs. In fact, allergies and conditions such as asthma are byproducts of an overactive immune system. These excessive immune responses can cause your airways to constrict and make it difficult to breathe. Some severe cases may require treatment to suppress the immune system.

During an active infection, however, the immune system is absolutely essential. When viruses infect your respiratory tract, immune cells are recruited to your lungs to fight off the infection. Although these cells are crucial to eliminate the virus from your body, their activity often results in collateral damage to your lung tissue. After the virus is removed, your body dampens your immune system to give your lungs a chance to recover.

Over the past decade, researchers have identified a variety of specialized stem cells in the lungs that can help regenerate damaged tissue. These stem cells can turn into almost all the different types of cells in the lungs depending on the signals they receive from their surrounding environment. Recent studies have highlighted the prominent role the immune system plays in providing signals that facilitate lung recovery. But these signals can produce more than one effect. They can not only activate stem cells, but also perpetuate damaging inflammatory processes in the lung. Therefore, your body tightly regulates when, where and how strongly these signals are made in order to prevent further damage.

While the reasons are still unclear, some people are unable to turn off their immune system after infection and continue to produce tissue-damaging molecules long after the virus has been flushed out. This not only further damages the lungs, but also interferes with regeneration via the lungs resident stem cells. This phenomenon can result in chronic disease, as seen in several respiratory viral infections including COVID-19, Middle East Respiratory Syndrome (MERS), respiratory syncytial virus (RSV) and the common cold.

In our review, my colleagues and I found that many different types of immune cells are involved in the development of chronic disease after respiratory viral infections, including long COVID-19.

Scientists so far have identified one particular type of immune cells, killer T cells, as potential contributors to chronic disease. Also known as cytotoxic or CD8+ T cells, they specialize in killing infected cells either by interacting directly with them or by producing damaging molecules called cytokines.

Killer T cells are essential to curbing the virus from spreading in the body during an active infection. But their persistence in the lungs after the infection has resolved is linked to extended reduced respiratory function. Moreover, animal studies have shown that removing killer T cells from the lungs after infection may improve lung function and tissue repair.

Another type of immune cells called monocytes are also involved in fighting respiratory infections, serving among the first responders by producing virus- and tissue-damaging cytokines. Research has found that these cells also continue to accumulate in the lungs of long COVID-19 patients and promote a pro-inflammatory environment that can cause further damage.

Understanding the immunological mechanisms underlying long COVID-19 is the first step to addressing a quickly worsening public health problem. Identifying the subtle differences in how the same immune cells that protect you during an active infection can later become harmful could lead to earlier diagnosis of long COVID-19. Moreover, based on our findings, my team and I believe treatments that target the immune system could be an effective approach to manage long COVID-19 symptoms. We believe that this strategy may turn out to be useful not only for COVID-19, but also for other respiratory viral infections that lead to chronic disease as well.

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Long COVID-19 and other chronic respiratory conditions after viral infections may stem from an overactive immune response in the lungs - The...

Abstract: To develop into the central nervous system, neuroepithelial cells must first form a neural tube consisting of a series of patterned neural progenitor cells along the anterior-posterior (AP) axis. Based on studies using model organisms, it has been revealed that AP spatial regionalization is dominated by gradients of morphogens that regulate retinoic acid (RA), sonic hedgehog (SHH), bone morphogenetic proteins (BMPs), and Wingless/int1 (WNT) signaling pathways. Recently, human pluripotent stem cells (hPSCs) were successfully induced into a patterned neural tissue with differential AP gene expression levels by a gradient of WNT activity controlled by a microfluidic device. However, the midbrain and hindbrain boundaries were not as sharp as observed in vivo, likely due to the lack of additional important morphogenic factors, such as RA and SHH. Here, we induced micropatterned hPSCs into AP patterned neural tissue by activating not only WNT but also RA and SHH signals under fully defined culture conditions. We found that hPSCs self-organized into spatially patterned midbrain (FOXG1-OTX2+) and hindbrain (HOXB4+) progenitors with a sharp boundary after 6 days of induction. Following the initial induction, the cells with midbrain identities near the pattern boundary folded inwardly to form a 3D structure, maintaining a distinct boundary between OTX2+ and HOXB4+ zones. To investigate the mechanism of cell fates patterning, we found that the reaction-diffusion of BMP/Noggin played a role in AP regionalization, while differential mechanical stress and cell sorting were unlikely to be involved. Then, we validated our model by investigating the effects of exposure to two known teratogens including valproic acid and isotretinoin. Drug treatment results successfully predicted that valproic acid inhibited the development of both midbrain and hindbrain development while isotretinoin disrupts the normal AP patterning of the midbrain and hindbrain. In conclusion, by integrating engineering approaches and chemically defined culture conditions, we have developed an in vitro AP patterned model of early human midbrain and hindbrain development, and we have revealed its potential to be employed as a high throughput drug discovery system.

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Self-organized anteroposterior regionalization of early midbrain and hindbrain using micropatterned human embryonic stem cells - Newswise